KLF2 regulates eNOS uncoupling via Nrf2/HO-1 in endothelial cells under hypoxia and reoxygenation.

08:00 EDT 27th March 2019 | BioPortfolio

Summary of "KLF2 regulates eNOS uncoupling via Nrf2/HO-1 in endothelial cells under hypoxia and reoxygenation."

Kruppel-like factor 2 (KLF2) regulates endothelial functions by modulating endothelial nitric oxide synthase (eNOS)/nitric oxide (NO) pathway. Tetrahydrobiopterin (BH) and S-glutathionylation of eNOS play essential roles in eNOS uncoupling and activation. However, the influence of KLF2 on eNOS uncoupling and the mechanism of eNOS activation still remain unknown. A hypoxia and reoxygenation (H/R) model of human umbilical vein endothelial cells (HUVECs) was utilized in this study. Cell viability and the eNOS uncoupling-related oxidative stress index were measured. The Nrf2 inhibitor ML385 and HO-1 siRNA were used to elucidate the mechanism of activation. The results show that overexpression of KLF2 increased the cell viability, reduced the lactate dehydrogenase leakage rate, downregulated the generation of O and ONOO, and increased NO levels and eNOS activity. Overexpression of KLF2 also increased the BH/BH ratio and the GSH/GSSG ratio, thus significantly improving eNOS uncoupling in the H/R model. KLF2 has no regulatory effect on the upstream-associated proteins in eNOS activation. However, when combined with the Nrf2 inhibitor or HO-1 siRNA, the regulatory effect of KLF2 on eNOS uncoupling was strongly reduced. These results suggest that KLF2 could improve eNOS uncoupling via Nrf2/HO-1 in H/R-induced endothelial injury.


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This article was published in the following journal.

Name: Chemico-biological interactions
ISSN: 1872-7786


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